m6A modification–mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability

Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppresso...

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Published inCancer science Vol. 113; no. 12; pp. 4135 - 4150
Main Authors Fang, Deliang, Ou, Xinde, Sun, Kaiyu, Zhou, Xingyu, Li, Youpei, Shi, Peng, Zhao, Zirui, He, Yulong, Peng, Jianjun, Xu, Jianbo
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.12.2022
John Wiley and Sons Inc
Subjects
1-Phosphatidylinositol 3-kinase
AKT protein
ALKBH5
Apoptosis
Cell cycle
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
CIP2A
Gastric cancer
Gene expression
Gene Expression Regulation, Neoplastic
Humans
Hybridization
Metastases
Metastasis
N6-methyladenosine
Non-coding RNA
Original
Phosphatase
Phosphatidylinositol 3-Kinases - metabolism
Phosphoprotein phosphatase
PI3K/AKT
Protein phosphatase
Proteins
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Stomach Neoplasms - pathology
TP53TG1
Tumor suppressor genes
Tumors
Ubiquitination
ALKBH5
CIP2A
gastric cancer
TP53TG1
PI3K/AKT
Online AccessGet full text

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Abstract Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination‐mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment. Reveal the important role of TP53TG1 as a tumor suppressor in inhibiting the progression of gastric cancer (GC). Explore the specific mechanism by which TP53TG1 binds to CIP2A and promotes its ubiquitination, thus inhibiting the activation of the PI3K/AKT pathway. Discover the new mechanism of TP53TG1 downregulation mediated by m6A methylation modification in GC.
AbstractList Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination-mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination-mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.
Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination‐mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.
Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination‐mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment. Reveal the important role of TP53TG1 as a tumor suppressor in inhibiting the progression of gastric cancer (GC). Explore the specific mechanism by which TP53TG1 binds to CIP2A and promotes its ubiquitination, thus inhibiting the activation of the PI3K/AKT pathway. Discover the new mechanism of TP53TG1 downregulation mediated by m6A methylation modification in GC.
Author Shi, Peng
Zhou, Xingyu
Peng, Jianjun
Fang, Deliang
Xu, Jianbo
Zhao, Zirui
Ou, Xinde
Li, Youpei
Sun, Kaiyu
He, Yulong
AuthorAffiliation 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou China
2 Laboratory of General Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou China
5 Digestive Disease Center, The Seventh Affiliated Hospital Sun Yat‐sen University Shenzhen China
4 Huazhong University of Science and Technology Union Shenzhen Hospital Shenzhen China
3 Department of Anesthesiology, Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
AuthorAffiliation_xml – name: 3 Department of Anesthesiology, Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
– name: 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou China
– name: 2 Laboratory of General Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou China
– name: 5 Digestive Disease Center, The Seventh Affiliated Hospital Sun Yat‐sen University Shenzhen China
– name: 4 Huazhong University of Science and Technology Union Shenzhen Hospital Shenzhen China
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36114757$$D View this record in MEDLINE/PubMed
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Copyright 2022 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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Keywords ALKBH5
CIP2A
gastric cancer
TP53TG1
PI3K/AKT
Language English
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2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Notes Deliang Fang, Xinde Ou, and Kaiyu Sun have contributed equally to this work and share first authorship.
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John Wiley and Sons Inc
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Snippet Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In...
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SubjectTerms 1-Phosphatidylinositol 3-kinase
AKT protein
ALKBH5
Apoptosis
Cell cycle
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
CIP2A
Gastric cancer
Gene expression
Gene Expression Regulation, Neoplastic
Humans
Hybridization
Metastases
Metastasis
N6-methyladenosine
Non-coding RNA
Original
Phosphatase
Phosphatidylinositol 3-Kinases - metabolism
Phosphoprotein phosphatase
PI3K/AKT
Protein phosphatase
Proteins
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Stomach Neoplasms - pathology
TP53TG1
Tumor suppressor genes
Tumors
Ubiquitination
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Title m6A modification–mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fcas.15581
https://www.ncbi.nlm.nih.gov/pubmed/36114757
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Volume 113
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